Ferrán Catalá-López

The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013

Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.

Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015

Importance Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions. Objective To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015. Design A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis. Main Outcomes and Measures Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year. Results Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). Loss of disability-adjusted life-years (DALYs) associated with SBP of at least 110 to 115 mm Hg increased from 148 million (95% UI, 134-162 million) to 211 million (95% UI, 193-231 million), and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg. Conclusions and Relevance In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher.

Epidemiology and Reporting Characteristics of Systematic Reviews of Biomedical Research: A Cross-Sectional Study.

Background Systematic reviews (SRs) can help decision makers interpret the deluge of published biomedical literature. However, a SR may be of limited use if the methods used to conduct the SR are flawed, and reporting of the SR is incomplete. To our knowledge, since 2004 there has been no cross-sectional study of the prevalence, focus, and completeness of reporting of SRs across different specialties. Therefore, the aim of our study was to investigate the epidemiological and reporting characteristics of a more recent cross-section of SRs. Methods and Findings We searched MEDLINE to identify potentially eligible SRs indexed during the month of February 2014. Citations were screened using prespecified eligibility criteria. Epidemiological and reporting characteristics of a random sample of 300 SRs were extracted by one reviewer, with a 10% sample extracted in duplicate. We compared characteristics of Cochrane versus non-Cochrane reviews, and the 2014 sample of SRs versus a 2004 sample of SRs. We identified 682 SRs, suggesting that more than 8,000 SRs are being indexed in MEDLINE annually, corresponding to a 3-fold increase over the last decade. The majority of SRs addressed a therapeutic question and were conducted by authors based in China, the UK, or the US; they included a median of 15 studies involving 2,072 participants. Meta-analysis was performed in 63% of SRs, mostly using standard pairwise methods. Study risk of bias/quality assessment was performed in 70% of SRs but was rarely incorporated into the analysis (16%). Few SRs (7%) searched sources of unpublished data, and the risk of publication bias was considered in less than half of SRs. Reporting quality was highly variable; at least a third of SRs did not report use of a SR protocol, eligibility criteria relating to publication status, years of coverage of the search, a full Boolean search logic for at least one database, methods for data extraction, methods for study risk of bias assessment, a primary outcome, an abstract conclusion that incorporated study limitations, or the funding source of the SR. Cochrane SRs, which accounted for 15% of the sample, had more complete reporting than all other types of SRs. Reporting has generally improved since 2004, but remains suboptimal for many characteristics. Conclusions An increasing number of SRs are being published, and many are poorly conducted and reported. Strategies are needed to help reduce this avoidable waste in research.

Inverse and direct cancer comorbidity in people with central nervous system disorders: a meta-analysis of cancer incidence in 577,013 participants of 50 observational studies

Background: There is a lack of scientific consensus about cancer comorbidity in people with central nervous system (CNS) disorders. This study assesses the co-occurrence of cancers in patients with CNS disorders, including Alzheimers disease (AD), amyotrophic lateral sclerosis (ALS), autism spectrum disorders, Downs syndrome (DS), Huntingtons disease (HD), multiple sclerosis (MS), Parkinsons disease (PD) and schizophrenia (SCZ). Method: Comprehensive search in PubMed/MEDLINE, Scopus and ISI Web of Knowledge of the literature published before March 2013. We identified 51 relevant articles from 2,229 discrete references, 50 of which contained data suitable for quantitative synthesis (577,013 participants). Pooled effect sizes (ES) were calculated using multiple random-effects meta-analyses. Sources of heterogeneity and uncertainty were explored by means of subgroup and sensitivity analyses, respectively. Results: The presence of CNS disorders was associated with a reduced co-occurrence of cancer (ES = 0.92; 95% confidence interval, CI: 0.87-0.98; I2 = 94.5%). A consistently lower overall co-occurrence of cancer was detected in patients with neurodegenerative disorders (ES = 0.80; 95% CI: 0.75- 0.86; I2 = 82.8%), and in those with AD (ES = 0.32; 95% CI: 0.22-0.46; I2 = 0.0%), PD (ES = 0.83; 95% CI: 0.76-0.91; I2 = 80.0%), MS (ES = 0.91; 95% CI: 0.87-0.95; I2 = 30.3%) and HD (ES = 0.53; 95% CI: 0.42-0.67; I2 = 56.4%). Patients with DS had a higher overall co-occurrence of cancer (ES = 1.46; 95% CI: 1.08-1.96; I2 = 87.9%). No association was observed between cancer and ALS (ES = 0.97; 95% CI: 0.76-1.25; I2 = 0.0%) or SCZ (ES = 0.98; 95% CI: 0.90-1.07; I2 = 96.3%). Patients with PD, MS and SCZ showed (a) higher co-occurrence of some specific cancers (e.g. PD with melanoma, MS with brain cancers and SCZ with breast cancer), and (b) lower co-occurrence of other specific cancers (e.g. lung, prostate and colorectal cancers in PD; lung and prostate cancers in MS; and melanoma and prostate cancer in SCZ). Conclusion: Increased and decreased co-occurrence of cancer in patients with CNS disorders represents an opportunity to discover biological and non-biological connections between these complex disorders.

The quality of reporting methods and results in network meta-analyses: an overview of reviews and suggestions for improvement.

Introduction Some have suggested the quality of reporting of network meta-analyses (a technique used to synthesize information to compare multiple interventions) is sub-optimal. We sought to review information addressing this claim. Objective To conduct an overview of existing evaluations of quality of reporting in network meta-analyses and indirect treatment comparisons, and to compile a list of topics which may require detailed reporting guidance to enhance future reporting quality. Methods An electronic search of Medline and the Cochrane Registry of methodologic studies (January 2004–August 2013) was performed by an information specialist. Studies describing findings from quality of reporting assessments were sought. Screening of abstracts and full texts was performed by two team members. Descriptors related to all aspects of reporting a network meta-analysis were summarized. Results We included eight reports exploring the quality of reporting of network meta-analyses. From past reviews, authors found several aspects of network meta-analyses were inadequately reported, including primary information about literature searching, study selection, and risk of bias evaluations; statement of the underlying assumptions for network meta-analysis, as well as efforts to verify their validity; details of statistical models used for analyses (including information for both Bayesian and Frequentist approaches); completeness of reporting of findings; and approaches for summarizing probability measures as additional important considerations. Conclusions While few studies were identified, several deficiencies in the current reporting of network meta-analyses were observed. These findings reinforce the need to develop reporting guidance for network meta-analyses. Findings from this review will be used to guide next steps in the development of reporting guidance for network meta-analysis in the format of an extension of the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analysis) Statement.

Prevalence of attention deficit hyperactivity disorder among children and adolescents in Spain: a systematic review and meta-analysis of epidemiological studies

BackgroundAttention deficit hyperactivity disorder (ADHD) is a commonly diagnosed neuropsychiatric disorder in childhood, but the frequency of the condition is not well established in many countries. The aim of the present study was to quantify the overall prevalence of ADHD among children and adolescents in Spain by means of a systematic review and meta-analysis.MethodsPubMed/MEDLINE, IME, IBECS and TESEO were comprehensively searched. Original reports were selected if they provided data on prevalence estimates of ADHD among people under 18 years old in Spain and were cross-sectional, observational epidemiological studies. Information from included studies was systematically extracted and evaluated. Overall pooled-prevalence estimates of ADHD were calculated using random-effects models. Sources of heterogeneity were explored by means sub-groups analyses and univariate meta-regressions.ResultsFourteen epidemiological studies (13,026 subjects) were selected. The overall pooled-prevalence of ADHD was estimated at 6.8% [95% confidence interval (CI) 4.9 – 8.8%] representing 361,580 (95% CI 260,550 – 467,927) children and adolescents in the community. There was significant heterogeneity (P < 0.001), which was incompletely explained by subgroup analyses and meta-regressions.ConclusionsOur findings suggest that the prevalence of ADHD among children and adolescents in Spain is consistent with previous studies conducted in other countries and regions. This study represents a first step in estimating the national burden of ADHD that will be essential to building evidence-based programs and services.

Network meta‑analysis for comparing treatment effects of multiple interventions: an introduction

Abstract Systematic reviews and meta-analyses of randomized trials have long been important synthesis tools for guiding evidence-based medicine. More recently, network meta-analyses, an extension of traditional meta-analyses enabling the comparison of multiple interventions, use new statistical methods to incorporate clinical evidence from both direct and indirect treatment comparisons in a network of treatments and associated trials. There is a need to provide education to ensure that core methodological considerations underlying network meta-analyses are well understood by readers and researchers to maximize their ability to appropriately interpret findings and appraise validity. Network meta-analyses are highly informative for assessing the comparative effects of multiple competing interventions in clinical practice and are a valuable tool for health technology assessment and comparative effectiveness research.

Control of arterial hypertension in Spain: a systematic review and meta-analysis of 76 epidemiological studies on 341 632 participants.

Objective Hypertension is a leading global risk factor for the burden of cardiovascular disease. Data about changes in hypertension control are important to set intervention priorities. We conducted a systematic review and meta-analysis of epidemiological studies to determine the control of hypertension in Spain over the past decade. Methods A search of PubMed/MEDLINE, SCOPUS and IME was performed for epidemiological studies conducted in Spain (since 2000) with data on control rates for hypertension. The primary outcome was the prevalence of uncontrolled hypertension defined as the percentage of patients having SBP at least 140 mmHg and/or DBP at least 90 mmHg. For populations at risk (e.g. patients with diabetes), the definition was SBP at least 130 mmHg and/or DBP at least 80–85 mmHg. Results Seventy-six studies evaluating 341 632 patients (79% with hypertension) met the inclusion criteria. Among hypertensive patients, the overall pooled prevalence of uncontrolled hypertension (≥140/90 mmHg) was 67.0% [95% confidence interval (CI) 64.1–69.9%], but was 87.6% (95% CI 86.2–89.0%) when the most restricted definition (≥130/80–85 mmHg) was used for patients at risk. The test for heterogeneity was significant (P < 0.001). Using metaregression analyses, we showed that the prevalence of uncontrolled hypertension did not change significantly over time, but the percentage of patients receiving at least two antihypertensive drugs increased (P = 0.032 and 0.001). Conclusion In Spain, the control of hypertension is far from optimum and does not appear to have improved in recent years despite the increased intensity of therapy. Patients at risk with comorbidities appear to be controlled worse.

The increasing burden of mental and neurological disorders.

In early 1990s, Murray and Lopez proposed a summary measure of population health to quantify population health losses combining both premature mortality and morbidity data, the so-called Disability Adjusted Life Years (DALYs) (World Bank, 1993; Murray and Lopez, 1996). Basically, one DALY is equivalent to the loss of one year of healthy life. DALYs allow the burden of disease in a population to be measured as the gap between current health and an ideal situation where everyone lives to old age, free of disease and disability. It is an indication of the unfinished health research agenda and identifies areas where health gains can be made (Mathers et al., 2000; Murray et al., 2002). The first Global Burden of Disease (GBD) 1990 study (Murray and Lopez, 1996) commissioned by the World Bank and the World Health Organization provided a comprehensive assessment of the burden of disease in terms of DALYs across a wide range of 131 diseases and 10 risk factors for the world and selected regions. As a consequence, mental and neurological disorders, among other conditions for which non-fatal outcomes are of particular relevance, were identified as being part of the leading causes of disease burden worldwide. Since then a number of initiatives have been undertaken with important implications for global health policy, research and clinical practice (UN, 2012; WHO, 2008, 2012). The recent publication (on Dec 2012) of the new GBD 2010 study (Murray et al., 2012) addresses key methodological limitations of previous studies, expands the scope and provides breakthrough epidemiological evidence that will revolutionize the global health agenda in the coming years. In the recent version of the study, it is worthy of note the global burden of mental and neurological disorders account for 10.4% of global DALYs in 2010, compared to 7.3% in 1990. Table 1 summarizes the estimated 10 leading categories of disease burden in 1990 and 2010 worldwide. On the other hand, among the top 50 leading mental and neurological specific causes of global DALYs are (in descending order), stroke (rank 3 although by convention contributes to burden of cardiovascular disorders), unipolar depression (rank 11), anxiety disorders (rank 26), migraine (rank 30), drug use

Sex Differences in Stroke Incidence, Prevalence, Mortality and DALYs: Results from the Global Burden of Disease Study 2013

Background: Accurate information on stroke burden in men and women are important for evidence-based healthcare planning and resource allocation. Previously, limited research suggested that the absolute number of deaths from stroke in women was greater than in men, but the incidence and mortality rates were greater in men. However, sex differences in various metrics of stroke burden on a global scale have not been a subject of comprehensive and comparable assessment for most regions of the world, nor have sex differences in stroke burden been examined for trends over time. Methods: Stroke incidence, prevalence, mortality, disability-adjusted life years (DALYs) and healthy years lost due to disability were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Data inputs included all available information on stroke incidence, prevalence and death and case fatality rates. Analysis was performed separately by sex and 5-year age categories for 188 countries. Statistical models were employed to produce globally comprehensive results over time. All rates were age-standardized to a global population and 95% uncertainty intervals (UIs) were computed. Findings: In 2013, global ischemic stroke (IS) and hemorrhagic stroke (HS) incidence (per 100,000) in men (IS 132.77 (95% UI 125.34-142.77); HS 64.89 (95% UI 59.82-68.85)) exceeded those of women (IS 98.85 (95% UI 92.11-106.62); HS 45.48 (95% UI 42.43-48.53)). IS incidence rates were lower in 2013 compared with 1990 rates for both sexes (1990 male IS incidence 147.40 (95% UI 137.87-157.66); 1990 female IS incidence 113.31 (95% UI 103.52-123.40)), but the only significant change in IS incidence was among women. Changes in global HS incidence were not statistically significant for males (1990 = 65.31 (95% UI 61.63-69.0), 2013 = 64.89 (95% UI 59.82-68.85)), but was significant for females (1990 = 64.892 (95% UI 59.82-68.85), 2013 = 45.48 (95% UI 42.427-48.53)). The number of DALYs related to IS rose from 1990 (male = 16.62 (95% UI 13.27-19.62), female = 17.53 (95% UI 14.08-20.33)) to 2013 (male = 25.22 (95% UI 20.57-29.13), female = 22.21 (95% UI 17.71-25.50)). The number of DALYs associated with HS also rose steadily and was higher than DALYs for IS at each time point (male 1990 = 29.91 (95% UI 25.66-34.54), male 2013 = 37.27 (95% UI 32.29-45.12); female 1990 = 26.05 (95% UI 21.70-30.90), female 2013 = 28.18 (95% UI 23.68-33.80)). Interpretation: Globally, men continue to have a higher incidence of IS than women while significant sex differences in the incidence of HS were not observed. The total health loss due to stroke as measured by DALYs was similar for men and women for both stroke subtypes in 2013, with HS higher than IS. Both IS and HS DALYs show an increasing trend for both men and women since 1990, which is statistically significant only for IS among men. Ongoing monitoring of sex differences in the burden of stroke will be needed to determine if disease rates among men and women continue to diverge. Sex disparities related to stroke will have important clinical and policy implications that can guide funding and resource allocation for national, regional and global health programs.